Abstract The overall goal of Project 1 is to examine the prognostic significance of mental stress-induced ischemia in a large and contemporary population of CAD patients with and without exercise-induced ischemia, and to examine the role of genetic variations in the a- and ^ff-adrenergic receptor genes and other gene systems known to regulate the reactivity response to stress. Specifically, we propose to address the following aims: Aim 1: Among CAD patients with and without exercise-induced ischemia, examine the relationship between mental stress-induced ischemia and adverse outcomes defined as: a) death and myocardial infarction (Ml); and b) a composite index of death, nonfatal Ml, hospitalization for unstable angina, and need for revascularization (coronary bypass surgery or percutaneous intervention). We will test the hypothesis that CAD patients with mental stress-induced ischemia will have higher rates of adverse outcomes than those without mental stress-induced ischemia irrespective of the presence of exercise-induced ischemia. Aim 2: Among CAD patients with and without exercise-induced ischemia, examine the relationship between genetic polymorphisms of the a- and ;ff-adrenergic receptors and other candidate genes related to the stress response and mental stress-induced ischemia. We will test the hypothesis that these genetic polymorphisms will be associated with mental stress-induced ischemia and thus the allele and/or genotype frequencies in CAD patients without mental stress-induced ischemia will differ from those in patients with mental stress-induced ischemia.